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Biomedical subjects

I Ziv

Publications and source records attributed to I Ziv.

At least 55 records · Page 3Linked to original sources
PubMed1997

Two waves of cyclin B and proliferating cell nuclear antigen expression during dopamine-triggered neuronal apoptosis.

The neurotransmitter dopamine is capable of inducing apoptosis in postmitotic sympathetic neurons via its oxidative metabolites. To detect genes whose expression is transcriptionally regulated during the early stages of dopamine-triggered apoptosis, we applied the differential display method to cultured sympathetic neurons. One of the up-regulated genes was identified as cyclin B2, which exhibited two waves of induction and destruction, both at the mRNA and protein levels, resembling the sequential oscillations typical of two successive mitotic events in proliferating cells. The time window between the two waves was characterized by a change in expression of other cell-cycle stage-specific genes, and oscillations in proliferating cell nuclear antigen and alterations in cyclin A were observed. Cyclin D1 and cyclin-dependent kinases were undetected and no sign of active DNA synthesis could be observed, indicating that activation of cell-cycle components is incomplete. In comparison with a normal cell cycle, temporal expression profile of these mediators was unsynchronized. Whereas the first wave of cell-cycle changes occurred prior to the commitment of the cells to the death process and could be tolerated by the cells, the second wave of changes coincided with the death commitment point. Our findings indicate that inappropriate and incomplete activation of some cell cycle-related genes in postmitotic neurons occurs during dopamine-triggered neuronal apoptosis.

Animals↗
PubMed1997

Muscle force and endurance in untreated and human growth hormone or insulin-like growth factor-I-treated patients with growth hormone deficiency or Laron syndrome.

Muscle force and endurance of four muscle groups (biceps, triceps, hamstrings and quadriceps) were measured by a computerized device in three groups: (A) 4 boys with isolated growth hormone deficiencies (IGHD) examined before at 10 and 24 months of hGH treatment; (B) 5 children (2 F, 3 M) with Laron syndrome were examined 3.5-4 years after initiation of insulin-like growth factor-I (IGF-I) treatment, and (C) comprised 8 untreated adults (5 F, 3 M) with Laron syndrome. For each patient, 2 matched controls, by age, sex, physical activity and height below the 50th percentile, were examined. GH- or IGF-I-deficient patients before treatment revealed reduced muscle force and endurance. GH treatment (0.6 U/kg/week) restored muscle force and endurance, progressively, mainly in the boys with puberty. Three to 4 years of IGF-I treatment (150 micrograms/kg/day) in patients with Laron syndrome proved to have a weaker effect than GH in restoring muscle force. The difference in effectiveness between hGH and IGF-I in restoring muscle force may be due to either the more marked muscle underdevelopment in Laron syndrome patients than in patients with IGHD or a difference in action potential between the two hormones.

Adolescent↗
PubMed1996

Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson's disease.

We have recently shown that dopamine (DA) can trigger apoptosis, an active program of cellular self-destruction, in various neuronal cultures and proposed that inappropriate activation of apoptosis by DA and or its oxidation products may initiate nigral cell loss in Parkinson's disease (PD). Since DA toxicity may be mediated via generation of oxygen-free radical species, we examined whether DA-induced cell death in PC12 cells may be inhibited by antioxidants. We have found that the thiol containing compounds, reduced glutathione (GSH), N-acetyl-cysteine (NAC), and dithiothreitol (DTT) were markedly protective, while vitamins C and E had lesser or no effect. The thiol antioxidants and vitamin C but not vitamin E, prevented dopamine autooxidation and production of dopamine-melanin. Their protective effect has also manifested by inhibiting DA-induced apoptosis; DNA fragmentation was prevented as was shown histochemically by the in situ end-labeled DNA technique (TUNEL). Intracellular GSH and other thiols constitute an important natural defense against oxidative stress. We have found that depletion of cellular GSH by the addition of phoron, a substrate of glutathione transferase, and buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl transpeptidase, significantly enhanced DA toxicity. Cotreatment with NAC rescued the cells from the toxic effect of BSO+DA, and phoron+ DA, while addition of GSH provided only partial protection from BSO+DA toxicity. Our data indicate that the thiol family of antioxidants, but not vitamins C and E, are highly effective in rescuing cells from DA-induced apoptosis. Further study of the mechanisms underlying the unique protective capacity of thiol antioxidants may lead to the development of new neuroprotective therapeutic strategies for PD.

Acetylcysteine↗
PubMed1996

Ultrasound velocity and broadband attenuation over a wide range of bone mineral density.

Ultrasound velocity (UV) and broadband ultrasound attenuation (BUA) were studied in human and bovine bone with a wide range of bone mineral density (BMD). The BMD of 98 fresh specimens was measured by quantitative computed tomography: 42 cancellous specimens from women in the age group of 64 +/- 4 years; 51 bovine cancellous and 5 bovine cortical. BMD values ranged from 90 to 400 mg/cm3 for the human cancellous bone, 310 to 870 mg/cm3 for the bovine cancellous bone, and 1750 to 1780 mg/cm3 for the bovine cortical bone. BMD showed a strong linear correlation with apparent density over the entire range of density (r = 0.979). UV of human and bovine cancellous bone was 1480-2650 m/s and 2880-3100 m/s for bovine cortical bone. BUA values were 1-61 dB/MHz/cm for the cancellous specimens and 5-12 dB/MHz/cm for cortical specimens. UV was found to be linear with BMD for all specimens; however, BUA was linear with BMD only for the specimens from elderly women. A quadratic relationship between BUA and BMD was found when the bovine samples were included.

Animals↗
PubMed1996

The accuracy of computed tomography-based linear measurements of human femora and titanium stem.

RATIONALE AND OBJECTIVES: The authors investigate the accuracy of computed tomography linear measurement of femora with titanium stem, and the effect of the stem on these measurements. MATERIALS AND METHODS: Two embedded cadaveric femora, one of them containing a titanium stem, and two cortical bone parallelepipeds were scanned. Thirty-six cross-sections were studied, each measured in two linear directions by the profile window technique. A half-maximum height method was used to determine the cortex-gap-titanium sizes from the computed tomography (CT) images. The accuracy of the measurements from the parallelepipeds, femora, and titanium stem taken from the CT was compared with those taken by a digital caliper of anatomical sections at the same level of the same bone. RESULTS: Computed tomography measurements of the parallelepipeds were similar to the anatomical size (mean relative error 0.04% +/- 0.63%). The mean error and mean relative error of the cadaveric femora CT with and without the stem were similar to the control parallelepipeds. Higher values of error were found for the titanium stem. CONCLUSIONS: The half-maximum height method in the profile window provides an accurate measurement of the femoral cortex and the titanium stem. The presence of the titanium stem in the medullary cavity of the femur did not interfere with the measurements of cortical dimensions.

Aged↗
PubMed1996

Fatigue in multiple sclerosis compared with chronic fatigue syndrome: A quantitative assessment.

Fatigue, a common complaint among patients with multiple sclerosis (MS), is poorly characterized. We developed a computerized method that quantitatively measures fatigue, and defined a fatigue index (FI), which is the ratio between the integral of muscle strength decay over time and maximal voluntary contraction. Thirty patients (mean age, 37.4 +/- 10.3 years) were examined - 20 patients with pyramidal tract involvement and 10 patients with involvement of other neurological systems. We evaluated 10 patients during relapse and 3 months afterwards, and compared their results with those of four patients with chronic fatigue syndrome (CFS) and 13 age-matched health subjects. The FI was significantly higher in the MS patients as compared with the CFS patients and normal controls: 34.2 +/- 6.4% versus 27.5 +/- 1.0% and 23.6 +/- 6.8%, p < 0.05. Within the MS group, the FI correlated with the presence of pyramidal signs- 43.5% compared with 33% in patients without pyramidal signs, p < 0.01. In MS patients, fatigue worsened during a relapse affecting the pyramidal tract, but not during a relapse in other systems. These results demonstrate that fatigue can be quantitatively measured in MS patients, and that pyramidal dysfunction leads to increased fatigability.

Adolescent↗
PubMed1996

Gastric emptying in Parkinson's disease: patients with and without response fluctuations.

Delayed gastric emptying may be an important pharmacokinetic mechanism underlying some of the response fluctuations that develop after long-term levodopa therapy. We performed a radionuclide gastric emptying study using a standard Tc-99m colloid-labeled solid meal in 30 patients with Parkinson's disease (PD), 15 fluctuators with "delayed-on" and "no-on" phenomena, and 15 nonfluctuators. Fasting patients were given the standard meal, and gastric emptying was monitored with a gamma camera positioned over the stomach, recording data for 1 hour. PD patients had prolonged gastric emptying measured after 60 minutes compared with the normal control subjects (70.7 +/- 16% versus < 60%). Gastric retention measured after 1 hour was increased in patients with fluctuations compared with patients without fluctuations (77.4 +/- 15.5% versus 64.0 +/- 14.3%; p < 0.05). Half-time emptying was significantly delayed in patients with, as compared with those without, response fluctuations (221 +/- 202 minutes versus 85 +/- 31 minutes; p < 0.05). This demonstrates that delayed gastric emptying is common in PD patients and is more marked in those with response fluctuations. The stomach is an important target organ in PD, affected either by the basic PD pathology, chronic drug administration, or both.

Adult↗
PubMed1996

The effect of ultrasonically determined anisotropy on longitudinal fracture of cortical bone.

This study examines the effects of density and microstructural anisotropy on longitudinal crack propagation in compact bone. Bovine cortical bone samples were demineralized by acid, producing specimens with a wide range of bone density. Ultrasound velocity was measured in the radial and longitudinal directions of each specimen using a pulse transmission technique. A proposed microstructural anisotropy parameter based on these ultrasound velocities was introduced and evaluated. The critical stress intensity factors K(IC) of these specimens were determined by mechanical fracture toughness tests. A linear regression study demonstrated that assessment of fracture toughness was precisely achieved by the combined effect of density and microstructural anisotropy of compact bone (r2 = 0.951, p < 0.0001).

Animals↗
PubMed1996

Impaired absorption of oral levodopa: a major cause for response fluctuations in Parkinson's disease.

Most patients with Parkinson's disease develop response fluctuations after several years of chronic treatment with levodopa. Accumulating evidence suggest that pharmacokinetic mechanisms are the cause of some subtypes of response fluctuations, especially the "delayed-on" and "no-on" phenomena. Evaluation of gastric emptying in Parkinson patients with and without response fluctuations revealed that those with fluctuations had a significant delay in gastric emptying compared to patients without fluctuations. Treatment with cisapride, a prokinetic drug, causes amelioration of these fluctuations. The optimal solution is to bypass the stomach completely and deliver levodopa parenterally. This was done by levodopa ethylester injections, which reduced latency to "on" and prolonged "on" duration in patients with severe response fluctuations. These data emphasize the role of the stomach as one of the causes for deterioration in Parkinson's disease.

Administration, Oral↗
PubMed1995

Dopamine-induced programmed cell death in mouse thymocytes.

Exposure of mouse thymocytes to dopamine caused apoptosis (programmed cell death). This was manifested by cellular condensation and membrane damage shown by flow cytometry measurements and scanning electron microscopic study. Dopamine also affected thymocytic nuclei and their genomic DNA integrity. Most of the DNA molecules accumulated in a subdiploid peak in flow cytometry analysis, indicating DNA fragmentation to small particles. DNA analysis showed the typical pattern of 'DNA ladder' caused by internucleosomal DNA cleavage. X-ray microanalysis of the cellular elements of dopamine-treated cells showed elevation of sodium (Na), chloride (Cl) and calcium (Ca) peaks, accompanied by reduction in phosphate (P) concentrations. Comparison of the potassium (K) and P concentrations showed significant differences between the two major death processes: necrosis (induced by exposure to sodium azide (NaN3)) and apoptosis (induced by dopamine). High concentrations of K indicated cell viability while reductions in P and elevations in Ca levels were found to be typical of apoptotic cell death. The antioxidant dithiothreitol (DTT) suppressed dopamine-induced apoptosis in thymocytes, suggesting that its toxicity may be mediated via generation of reactive oxygen radicals. Our study suggests that under certain circumstances, dopamine and/or its metabolites, may induce a process of apoptotic cell death of the dopamine-producing cells in the substantia nigra. Increased accessibility of dopamine to the nigral cell nucleus or inability to scavenge excess free radicals generated from dopamine oxidation triggering programmed cell death, may cause the progressive nigral degeneration in Parkinson's disease.

Animals↗
PubMed1995

Effect of cisapride on response fluctuations in Parkinson's disease.

Impaired gastric emptying may be the cause for some response fluctuations in Parkinson's disease (PD), especially the "delayed-on" and "no-on" phenomena. Cisapride is a prokinetic drug that enhances gastric emptying by releasing acetylcholine from the myenteric plexus. Tolerability and safety as well as efficacy of cisapride was studied in an open-label trial on 15 fluctuating PD patients. Twelve patients had "delayed-on" and six had "no-no" phenomena. They filled out daily diaries on times of levodopa intake and of turning "on" and "off" for 1 week on levodopa alone and for an additional week of pretreatment with cisapride, 30 min before early morning, early afternoon, and late evening doses of levodopa. Cisapride significantly shortened latency to "on" from 60 +/- 20 to 45 +/- 19 min after the morning dose and from 63 +/- 17 to 47 +/- 22 min after the evening doses. Patients with "no-no" phenomenon had a decreased number of dose failures from 23 before to nine during cisapride treatment. The drug was well tolerated, with no important side effects. Our study supports the role of impaired gastric emptying in some subtypes of motor fluctuations and indicates that they may be improved by prokinetic drugs.

Aged↗
PubMed1995

Lymphocyte ultrastructure in patients with multiple sclerosis.

The present study was undertaken to examine the ultrastructure of the lymphocytes of patients with relapsing-remitting multiple sclerosis (RRMS) and to compare it to that of the lymphocytes of multiple sclerosis (MS) patients treated with intravenously administered immunoglobulin 0.4 mg/kg of body weight for 5 consecutive days followed by booster doses of immunoglobulin 0.4 mg/kg every two months for a total of 12 months. Peripheral blood lymphocytes of healthy volunteers served as control. The results indicate that lymphocytes of untreated patients differ markedly by both ultrastructure, as well as the number and size of their mitochondria. Since most of these changes disappeared following treatment, it is suggested that they are an expression of lymphocyte activation in this disease.

Adolescent↗
PubMed1995

IL-3-LA production by mononuclear cells of patients with multiple sclerosis: effect of treatment with intravenous immunoglobulins.

IL-3-like activity (IL-3-LA) is a growth factor that stimulates stem cell maturation. We examined the production of IL-3-LA by peripheral blood mononuclear cells of 10 patients with relapsing-remitting multiple sclerosis (MS) following one year of treatment with intravenous immunoglobulins (IVIG). The results were compared with those obtained in 13 age- and sex-matched untreated patients with relapsing-remitting MS and in 14 healthy controls. IL-3-LA was assayed using the IL-3-dependent 32-D-cl-23 murine cell line. IL-3-LA production was 60% higher in untreated MS patients than in healthy controls (134 +/- 19 u/ml and 78.7 +/- 15.9 u/ml, respectively; p < 0.01), and lower in patients treated with IVIG than in untreated patients (101.4 +/- 4.9 u/ml; p < 0.02). IL-3-LA production also decreased after incubation of mononuclear cells with IVIG of both untreated MS patients and controls. This study indicates a possible beneficial effect of IVIG on the immunological status of MS patients.

Adolescent↗
PubMed1995

Ocular effects of hyoscine in double dose transdermal administration and its reversal by low dose pyridostigmine.

The potential of low dose (30 mg t.i.d) pyridostigmine to reduce the ocular side effects of double dose transdermal controlled release hyoscine was evaluated by the study of near visual acuity, accommodation amplitude and pupil diameter in a placebo controlled, double masked study. We studied 47 healthy men (age 18-21 yr) in 3 groups: 16 assigned to placebo hyoscine and placebo pyridostigmine, 15 assigned to double dose hyoscine and placebo pyridostigmine, and 16 to double dose hyoscine and pyridostigmine. Subjects were tested during 48 h of treatment and 48 h of washout period. Blood cholinesterase inhibition level and amount of hyoscine released from the patches were used as parameters of reliability. Difference between groups was assessed using change from baseline scores. Double dose hyoscine caused decrease in near visual acuity to a mean of 14/18. Accommodation amplitude was decreased in the double dose transdermal hyoscine group from 9.19 +/- 1.04 to 4.83 +/- 1.97 diopters of accommodation. This decrease was significant when compared to the placebo group (p < 0.05) and to the pyridostigmine-protected group (p < 0.05). Pyridostigmine, however, did not significantly change the hyoscine-induced mydriasis of 1.47 + 0.15 mm change from baseline (p < 0.05). These results suggest that pyridostigmine administration may be beneficial in shortening recovery time when near vision impairment is experienced following single and double dose transdermal hyoscine administration.

Adolescent↗
PubMed1994

Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons--a possible novel pathogenetic mechanism in Parkinson's disease.

We report that exposure of cultured, postmitotic chick-embryo sympathetic neurons, to physiological concentrations of dopamine (0.1-1 mM) for 24 h initiates a cellular death process characteristic of apoptosis (= programmed-cell-death, PCD). Dopamine caused marked morphological alterations, mainly axonal disintegration and severe shrinkage and condensation of cell bodies. Flow-cytometric analysis of propidium-iodide-stained cell nuclei revealed the characteristic apoptotic nuclear fragmentation: increase in nuclear granularity and emergence of a large, distinct population of nuclei with reduced DNA content (subdiploid, apoptotic peak). These alterations were similar to changes induced by nerve growth factor (NGF) deprivation, a model of sympathetic neuronal PCD. Alterations were inhibited by the anti-oxidative agent DTT. Inappropriate, dopamine-induced activation of PCD might have a role in nigral neuronal degeneration in Parkinson's disease.

Animals↗